S-Adenosylmethionine synthase

The ratio of peaks for peptides derived from 42 high abundance yeast proteins was examined for the wild type versus cln2 mutant strains (Oda et al., 1999). Only two of the proteins, a peroxisomal membrane protein and S-adenosylmethionine synthase 2, exhibited significant differences in expression between the strains. The biological significance of this observation is not yet known but the study does indicate that changes of >20% in expression levels can be detected using the technique (Oda et al., 1999). 

Cysteine Methionine S-Adenosylmethionine synthase a-Methyltransferase S-Adenosylhomocysteinase Cystathionine- /3-synthase Cystathionine- y- lyase... 

Dinuclear Cu11—Viv complexes exhibit ferromagnetic coupling for the single unpaired electron in the d9 and d1 ions.706 Other heterodinuclear complexes in which superhyperfine coupling has been observed include the dinuclear Vlv—Tl1 enzyme complexes in pyruvate kinase707 and S-adenosylmethionine synthase.708... 

S-adenosylmethionine carboxylase is the source of the propylamine in the polyamines spermine and spermidine. The activity of spermine synthase introduces this into spermidine and spermine, which has already been noted. It is worth pointing out that, whereas the inducible histidine decarboxylase... 

The best characterized B 12-dependent methyltransferases is methionine synthase (Figure 15.11) from E. coli, which catalyses the transfer of a methyl group from methyltetrahydrofolate to homocysteine to form methionine and tetrahydrofolate. During the catalytic cycle, B12 cycles between CH3-Co(in) and Co(I). However, from time to time, Co(I) undergoes oxidative inactivation to Co(II), which requires reductive activation. During this process, the methyl donor is S-adenosylmethionine (AdoMet) and the electron donor is flavodoxin (Fid) in E. coli, or methionine synthase reductase (MSR) in humans. Methionine synthase... 

ACC 71 synthase, i. e. (S)-adenosylmethionine methylthioadenosine lyase (EC 4.4.1.14), has been purified from several plant tissues [116]. Recently, ACC synthase cDNA clones have been isolated and sequenced from wounded fruit tissues of tomato, winter squash, zucchini, ripening apple and tomato fruit. Using the polymerase chain reaction (PCR), four different ACC synthase gene fragments were obtained by amplification of cDNA derived from mRNA of tomato... 

The unusual amino acid, 1-aminocyclopropanecarboxylic acid, a precursor of the phytohormone ethylene, is biosynthesized in plants from S-adenosylmethionine. By using dideuterated S-adenosylmethionine, the reaction, under the influence of a pyridoxal phosphate dependent synthase, involves an inversion at the x-carbon center (a feature rarely observed for pyridoxal phosphate reactions), leading to (5)-l-amino-2,2-dideuterocyclopropanecarboxylic acid4. 

Write out a plausible step-by-step mechanism by which 1-aminocyclopropane-l-carboxylate synthase (ACC synthase) of plant tissues can form ACC from S-adenosylmethionine. This reaction requires a specific cofactor... 

Ornithine decarboxylase is specifically inhibited by the enzyme-activated inhibitor a-difluoromethyl-ornithine, which can cure human infection with Trypanosoma brucei (African sleeping sickness) by interfering with polyamine synthesis.243-2443 In combination with inhibitors of spermidine synthase or S-adenosylmethionine decarboxylase,245 it can reduce polyamine levels and growth rates of cells. Another powerful inhibitor that acts on both ornithine and adenosylmethionine decarboxylases is the hydroxy-lamine derivative l-aminooxy-3-aminopropane 246... 

The most recent discoveries in the methionine to ethylene pathway are the demonstration of S-adenosylmethionine as the intermediate and the existence of the multigene family of ACC synthases that convert S-adenosylmethionine to ACC (for review see Kende, 1993). The expression of the different genes in different tissues is determined by different stimuli such as ripening, tissue wounding or the status of cell growth responses. The isolation of the oxidase enzyme that converts ACC to liberate the free ethylene molecule in vitro (Ververidis and John, 1991) was another breakthrough, particularly because for many years it was thought that the enzymes concerned would operate only on an intact membrane system in vivo. 

The final reaction, catalyzed by biotin synthase, involves the insertion of sulfur between the unreactive methyl and methylene carbons of dethiobiotin. The enzyme has an iron-sulfur box, and requires NADPff and a ferredoxin or flavo-doxin reducing system. S-Adenosylmethionine is also required, and is cleaved to yield methionine and a 5 -deoxyadenosyl radical during the reaction. Biotin synthase is a member of the radical SAM family of enzymes, in which the catalytic 5 -deoxyadenosyl radical is formed from S-adenosylmethionine,... 

The [Fe4S4(LS3)(SR )] cluster has been shown to engage in an electrophilic attack of the sulfonium ion, while causing reductive cleavage of the cofactor S-adenosylmethionine. This behavior is analogous to the enzymatic action of biotin synthase and other enzymes in the S-adenosylmethionine family see Iron-Sulfur Proteins). ... 

Uracil, produced by the pyrimidine synthesis pathway, is not a component of DNA. Rather, DNA contains thymine, a methylated analog of uracil. Another step is required to generate thymidylate from uracil. Thymidylate synthase catalyzes this finishing touch deoxyuridylate (dUMP) is methylated to thymidylate (TMP). As will be discussed in Chapter 27. the methylation of this nucleotide facilitates the identification of DNA damage for repair and, hence, helps preserve the integrity of the genetic information stored in DNA. The methyl donor in this reaction is N, N methylenetetrahydrofolate rather than -S-adenosylmethionine. 

Figure 7-10. Amino acids that can be converted to succinyl CoA. The amino acids methionine, threonine, isoleucine, and valine, which form succinyl CoA via methylmalonyl CoA, are all essential. The carbons of serine are converted to cysteine and do not form succinyl CoA by this pathway. A defect in cystathionine synthase (M) causes homocystinuria. SAM= S-adenosylmethionine PLP = pyridoxal phosphate.

Figure 8 Extended folate metabolism, including compartmentation. MTHFR, methylenetetrahydrofolate reductase SHMT, serine hydroxymethyltransferase BHMT, betaine homocysteine methyltransferase, MAT, methionine adenosyltransferase SAH-hydrolase, S-adenosylhomocysteine hydrolase MT, methyltransferase CBS, cystathionine /i-synthase SAM, S-adenosylmethionine SAH, S-aden-osylhomocysteine THF, tetrahydrofolate and 5-MeTHF, 5-methyltetrahydrofolate. (Reproduced from Van der Put etal. (2001) Folate, homocysteine and neural tube defects An overview. Experimental Biology and Medicine 226 243-270.)...

Methionine, homocysteine, and cysteine are linked by the methylation cycle and transsulfuratlon pathway (Figure 55-9). Conversion of methionine into homocysteine proceeds via the formation of S-adenosyl intermediates including S-adenosylmethionine, die methyl group donor in a wide range of transmethylation reactions. Homocysteine is further condensed with serine by cystathionine 3-synthase to form cystathionine. 

Fig. 3 Structural features of methionine synthase. Methionine synthase is comprised of five domains, which bind homocysteine (HCY), methylfolate (5-methyl THF), cobalamin, and S-adenosylmethionine (SAM). The Cap domain restricts oxidation of cobalamin in its vulnerable Cbl(I) state. Strucmres from E.coli (Bandarian et al., 2002 Dixon et al. 1996) and T.maritima (Evans et al. 2004) (PDB codes 1Q8J, 1K98 and IMSK, respectively) were used to construct this composite model. An uncharacteiized linker segment between the folate and cap domains is absent...

Dixon MM, Huang S, Matthews RG, Ludwig M. (1996) The structure of the C-terminal domain of methionine synthase presenting S-adenosylmethionine for reductive methylation of B12. Structure 4 1263-1275. 

F/gwre J. Installation of alkyl branches into polyketides by (A) and (B) noniterative type I PKSs or (C) and (D) AT4ess PKSs. ( ), methyl group of S-adenosylmethionine origin ACP, acyl carrier protein AT, malonyl CoA specific acyltransferase ATmm methylmalonyl CoA-specific acyltransferase Tfno, methoxymalonyl ACP-specific acyltransferase KS, ketoacyl synthase MT, methyltransferase SAM, S-adenosylmethionine. 

Dufe, V. T., Qiu, W., Muller, I. B., Hui, R., Walter, R. D., and Al-Karadaghi, S. (2007). Crystal structure of Plasmodium falciparum spermidine synthase in complex with the substrate decarboxylated S-adenosylmethionine and the potent inhibitors 4MCHA and Ado-DATO. ]. Mol. Biol. 373,167-177. 

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